β-catenin S45F mutation results in apoptotic resistance

Braggio, Danielle; Zewdu, Abeba; Londhe, Priya; Yu, Peter Y.; López, Gonzalo; Batte, Kara; Koller, David; Faria, Fernanda Costas Casal de; Casadei, Lucia; Strohecker, Anne M.; Lev, Dina; Pollock, Raphael E.

doi:10.1038/s41388-020-1382-5

Cited by 23 publications

(20 citation statements)

References 44 publications

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“…Previous studies suggested the contribution of this genetic alteration to resistance to targeted therapy [ 24 ] as well as immunotherapy [ 25 ]. The potential mechanism of melanoma insensitivity to treatment may involve resistance of the mutated cells to apoptosis [ 26 ]. A TP53 mutation may also impair a response to targeted therapy [ 27 ] and immunotherapy [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

NGS Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Melanoma Samples Using Oncomine™ Pan-Cancer Cell-Free Assay

Olbryt

Rajczykowski

Bal

et al. 2021

Genes

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Next-generation sequencing (NGS) in liquid biopsies may contribute to the diagnosis, monitoring, and personalized therapy of cancer through the real-time detection of a tumor’s genetic profile. There are a few NGS platforms offering high-sensitivity sequencing of cell-free DNA (cfDNA) samples. The aim of this study was to evaluate the Ion AmpliSeq HD Technology for targeted sequencing of tumor and liquid biopsy samples from patients with fourth-stage melanoma. Sequencing of 30 samples (FFPE tumor and liquid biopsy) derived from 14 patients using the Oncomine™ Pan-Cancer Cell-Free Assay was performed. The analysis revealed high concordance between the qPCR and NGS results of the BRAF mutation in FFPE samples (91%), as well as between the FFPE and liquid biopsy samples (91%). The plasma-tumor concordance of the non-BRAF mutations was 28%. A total of 17 pathogenic variants in 14 genes (from 52-gene panel), including TP53, CTNNB1, CCND1, MET, MAP2K1, and GNAS, were identified, with the CTNNB1S45F variant being the most frequent. A positive correlation between the LDH level and cfDNA concentration as well as negative correlation between the LDH level and time to progression was confirmed in a 22-patient cohort. The analysis showed both the potential and limitations of liquid biopsy genetic profiling using HD technology and the Ion Torrent platform.

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Section: Discussionmentioning

confidence: 99%

NGS Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Melanoma Samples Using Oncomine™ Pan-Cancer Cell-Free Assay

Olbryt

Rajczykowski

Bal

et al. 2021

Genes

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show abstract

“…Briefly, binding of Wnt ligands initiates this canonical pathway, inducing translocation of the nuclear localization of beta-catenin and activating wnt downstream targets to potentiate cell growth, adhesion and survival (45). Deregulated expression of wnt/beta-catenin has been reported in different cancer progression and therapeutic tolerance (46)(47)(48). In addition, dysregulation of apical junction is tightly connected with EMT (49), which contributes to the flexibility of cell motility and tissue regeneration.…”

Section: Discussionmentioning

confidence: 99%

Gene Panel of Persister Cells as a Prognostic Indicator for Tumor Repopulation After Radiation

et al. 2020

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Tumor repopulation during cycles of radiotherapy limits the radio-response in ensuing cycles and causes failure of treatment. It is thus of vital importance to unveil the mechanisms underlying tumor repopulating cells. Increasing evidence suggests that a subpopulation of drug-tolerant persister cancer cells (DTPs) could survive the cytotoxic treatment and resume to propagate. Whether these persister cells contribute to development of radio-resistance remains elusive. Based on the genetic profiling of DTPs by integrating datasets from Gene Expression Omnibus database, this study aimed to provide novel insights into tumor-repopulation mediated radio-resistance and identify predictive biomarkers for radio-response in clinic. A prognostic risk index, grounded on four persister genes (LYNX1, SYNPO, GADD45B, and PDLIM1), was constructed in non-small-cell lung cancer patients from The Cancer Genome Atlas Program (TCGA) using stepwise Cox regression analysis. Weighted gene co-expression network analysis further confirmed the interaction among persister-gene based risk score, radio-response and overall survival time. In addition, the predictive role of risk index was validated in vitro and in other types of TCGA patients. Gene set enrichment analysis was performed to decipher the possible biological signaling, which indicated that two forces behind persister cells, stress response and survival adaptation, might fuel the tumor repopulation after radiation. Targeting these persister cells may represent a new prognostic and therapeutic approach to enhance radio-response and prevent radio-resistance induced by tumor repopulation.

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“…Previous studies indicate that β-catenin-TCF/LEF interaction in cytoplasm can promote the transcription of downstream target genes and causes abnormal proliferation and differentiation of cells, thus promoting the occurrence of cancer (17,18). Actually, the site mutation of CTNNB1 always associate with the changes of CTNNB1 biological function in various humane diseases (19)(20)(21). A previous study shows that the CTNNB1 mutations trigger the high expression of Wnt signaling pathway, which further contribute to the development of LUAD (22).…”

Section: Original Articlementioning

confidence: 99%

CTNNB1 S37C mutation causing cells proliferation and migration coupled with molecular mechanisms in lung adenocarcinoma

Zhou¹,

Jin²,

Li³

et al. 2021

Ann Transl Med

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Background: This study aimed to investigate the potential cytological effects and molecular mechanisms of β-catenin (CTNNB1) S37C mutation in lung adenocarcinoma (LUAD).Methods: CTNNB1 with S37C mutation were transfected into LUAD cell lines. The expression of β-catenin were determined using Western blot. Cell proliferation and migration were detected using cell counting kit-8 (CCK-8) assay and wound healing assay, respectively. Transcriptome sequencing was performed on LUAD cells with CTNNB1 S37C mutation (CTNNB1 mutation group) and LUAD cells without treatment (Control group), followed by the screening of differentially expressed genes (DEGs).Functional enrichment analysis and protein-protein interaction (PPI) analysis were performed for the DEGs.Finally, the expression of key DEGs were validated by quantitative real-time PCR (qRT-PCR).Results: CTNNB1 with S37C mutation was successful expressed in 2 cell lines. Cells proliferation and migration were significantly promoted in mutation group in comparison with that of Control group (P<0.05).A total of 180 DEGs were revealed between Control and CTNNB1 mutation groups. These DEGs were mainly enriched in extracellular matrix function and nicotine addiction pathway. PPI network contained 51 DEGs and 45 interactions. PTPRD, GNG7 and CNTN1 were hub genes in PPI network with higher degree. CGB5 interacted with PTPRU, while IGFBP3 showed interaction with MMP1. Results of qRT-PCR confirmed the expression of several key DEGs in transcriptome analysis.Conclusions: CTNNB1 S37C mutation contributed the LUAD cells proliferation and migration. PTPRD, IGFBP-3, MMP1 and PTPRU might play roles in the effect of CTNNB1 S37C mutation in LUAD.

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β-catenin S45F mutation results in apoptotic resistance

Cited by 23 publications

References 44 publications

NGS Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Melanoma Samples Using Oncomine™ Pan-Cancer Cell-Free Assay

NGS Analysis of Liquid Biopsy (LB) and Formalin-Fixed Paraffin-Embedded (FFPE) Melanoma Samples Using Oncomine™ Pan-Cancer Cell-Free Assay

Gene Panel of Persister Cells as a Prognostic Indicator for Tumor Repopulation After Radiation

CTNNB1 S37C mutation causing cells proliferation and migration coupled with molecular mechanisms in lung adenocarcinoma

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